Harvard Medical School, Department of Systems Biology
Alpert Building, Room 425
200 Longwood Ave
Boston, MA 02115
Lab Size: Between 10 and 15
Life in single cells is dictated by chance: reactions that involve small numbers of molecules generate spontaneous fluctuations that then enslave all dependent processes. Our goal is to identify and understand the guiding principles behind such phenomena, by developing mathematical methods to interpret fluctuations, experimental methods to count molecules in single cells, and combining the two to study the simplest natural and engineered networks, primarily in bacteria and yeast cells. The mathematical methods focus more on general theorems for fluctuations than individual models, drawing on probability theory and statistical physics, as well as control and information theory. Our efforts particularly focus on analytical methods to interpret fluctuations in terms of physical observables rather than kinetic parameters. The experimental methods focus on various tricks from genetics and biochemistry to count the integer number of macromolecules in cells, combined with techniques from microfluidics and single molecule detection under the microscope. The applications range from stress response, replication control, partitioning of molecules at cell division, horizontal gene transfer, bacterial epigenetics, toxin-antitoxin systems, stochastic proteolysis, and the evolution of cooperation.
Landgraf, D., Okumus, B., Chien, P., Baker, T.A., & Paulsson, J. (2012). Segregation of molecules at cell division reveals native protein localization. Nature Methods, 9(5), 480-2. PMID: 22484850.
Tal, S. & Paulsson, J. (2012). Evaluating quantiative methods fo rmeasuring plasmid copy numbers in single cells. Plasmid, 67(2), 167-73. PMID: 22305922.
Huh, D. & Paulsson, J. (2011). Random partitioning of molecules at cell division. Proceedings of the National Academy of Sciences of the United States of America, 108(36), 15004-9. PMID: 1873252. PMCID: PMC3169110.
Hilfinger, A. & Paulsson, J. (2011). Separating Intrinsic from Extrinsic Fluctuations in Dynamic Biological Systems. Proceedings of the National Academy of Sciences of the United States of America, 108(29), 12167-12172. PMID: 21730172.
Huh, D & Paulsson, J (2011). Non-genetic heterogeneity from stochastic partitioning at cell division. Nature Genetics, 43(2), 95-100. PMID: 21186354.